It is generally known and accepted in the art that COMT inhibitors are useful in the treatment of Parkinson's disease. COMT inhibitors have been shown to be effective in clinical use for the treatment of Parkinson's disease as an adjunct to levodopa therapy. In order to achieve a steady plasma concentration of levodopa, it is desirable that the COMT inhibitor has a good bioavailability and a long duration of action. However, the commercially available COMT inhibitors are associated with a rather short duration of action and their oral bioavailability is limited.
COMT inhibitors have also been indicated to be useful in the treatment of, for example, hypertension, heart failure and depression (cf. e.g. U.S. Pat. No. 5,446,194) as well as inhibitors for the prevention of diabetic vascular dysfunctions (cf. U.S. Pat. No. 6,207,706). COMT inhibitors have also been disclosed as being useful for treating or controlling pain (cf. U.S. Pat. No. 6,723,754) as well as for treating restless legs syndrome (RLS), which is also known as Ekbom's syndrome (cf. WO 2006/051154). RLS is characterized by an irresistible urge to move the legs accompanied by other unpleasant sensations deep within the legs.
Some compounds with COMT inhibiting activity are known in the art. For example, catechol derivatives as COMT inhibitors have been disclosed e.g. in U.S. Pat. No. 5,389,653; U.S. Pat. No. 5,446,194; U.S. Pat. No. 6,150,412; U.S. Pat. No. 6,512,136; WO 01/98250; WO 01/98251; WO 02/02548; U.S. Pat. No. 6,903,114, WO 2004/112729 and WO 2005/058228. Isoflavone derivatives as COMT inhibitors have been disclosed in U.S. Pat. No. 3,973,608.
As to known benzofused five-membered heterocycles, 2-benzyl-7-bromo-6-nitro-benzofuran-4,5-diol has been disclosed in Lyubchanskaya et al. Khimiko-Farmatsevticheskii Zhurnal, 23 (1989) 843.